The mammalian ovary contains a large reservoir of non-growing primordial follicles. Very little is understood about the mechanisms governing activation of these follicles into the pool of growing follicles and growth of early preantral follicles. We have developed a culture system that supports activation of primordial follicles in organ cultures of bovine and baboon ovarian cortex; however, very few of these follicles grow to the secondary stage even after 20 days in culture. We have also developed a method for grafting cortical pieces beneath the chorioallantoic membrane (CAM) of 6-day-old chick embryos. The CAM grafts are quickly vascularized and spontaneous activation is inhibited. These two unique experimental models provide exciting opportunities to investigate the mechanisms that control activation of primordial follicles and preantral follicle growth. Therefore, I propose to further characterize ovarian cortical culture and CAM grafts as models for studying follicular activation and early growth (Specific Aim #1). I will also use these two exciting experimental models to determine whether kit ligand stimulates activation of primordial follicles (Specific Aim #2), and to examine the roles of growth hormone and growth differentiation factor-9 in growth of early preantral follicles (Specific Aim #3). The ultimate goals of this research are to elucidate fundamental mechanisms that may lead to new contraceptive technologies, new methods for alleviating infertility, and a better understanding of mechanisms of follicle depletion (menopause).